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Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies

  • Henry A. Nasrallah (a1), Josephine B. Cucchiaro (a2), Yongcai Mao (a2), Andrei A. Pikalov (a2) and Antony D. Loebel (a2)...

Abstract

Objective

Depressive symptoms are common in schizophrenia and can worsen outcomes and increase suicide risk. Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia and for the treatment of major depressive episodes associated with bipolar I disorder. This post hoc analysis evaluated the effect of lurasidone on depressive symptoms in patients with schizophrenia.

Methods

Patient-level data were pooled from 4 similarly designed, double-blind, placebo-controlled, 6-week registration studies of lurasidone (40–160 mg/d) in adult patients with an acute exacerbation of schizophrenia. Changes in depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), were analyzed for the overall sample and for subgroups of patients stratified by baseline MADRS scores.

Results

MADRS assessments at baseline and endpoint (day 42 or last observation carried forward [LOCF]) were available for 1330 patients. Patients receiving lurasidone experienced significantly greater decreases in MADRS score (–2.8, least-squares [LS] mean change, LOCF) compared with patients receiving placebo (–1.4, P < .001, effect size 0.24). Analysis of change in MADRS score (LOCF) by baseline symptom severity (MADRS score of ≥12, ≥14, ≥16, ≥18) showed significantly greater improvement for lurasidone-treated patients across all severity groups; effect sizes ranged from 0.25 to 0.34. Among patients with a baseline MADRS score of ≥12, depressive symptom remission (defined as MADRS score <10 at LOCF endpoint) was attained by 45.0% of lurasidone-treated patients and 36.3% of patients receiving placebo (P < .05).

Conclusions

In a pooled analysis of short-term, placebo-controlled studies, lurasidone significantly improved depressive symptoms in patients with schizophrenia.

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Copyright

The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence http://creativecommons.org/licenses/by/3.0/

Corresponding author

*Address for correspondence: Henry A. Nasrallah, MD, Department of Neurology and Psychiatry, 1438 S. Grand Blvd, St. Louis, MO 63104, USA. (Email: hnasral@slu.edu)

Footnotes

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Nancy Holland, PhD, Synchrony Medical Communications, LLC, provided medical writing and editorial assistance for this manuscript under the direction of the authors. Financial support for this writing and editing assistance from Synchrony Medical Communications, LLC, was provided by Sunovion Pharmaceuticals Inc., Marlborough, MA. Clinical research was sponsored by Sunovion Pharmaceuticals Inc; the sponsor was involved in design, collection, analysis, interpretation, and accuracy of data. The content of this manuscript, the interpretation, and the decision to submit this manuscript for publication in CNS Spectrums were made by the authors independently.

Portions of this analysis were presented at the annual meeting of the American Psychiatric Association, May 5–9, 2012, Philadelphia, PA, USA, and the 14th International Congress on Schizophrenia Research, April 21–25, 2013, Orlando, FL, USA.

ClinicalTrials.gov identifiers: NCT00088634 (Study D1050196), NCT00549718 (Study D1050229), NCT00615433 (Study D1050231), NCT00790192 (Study D1050233). All trials were registered in the ClinicalTrials.gov database.

Footnotes

References

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